The placenta supports the exchange of nutrients and gases between mother and fetus. Trophoblasts are the parenchymal cells of the placenta and perform the vast majority of its functions. There are different types of trophoblasts derived from stem cells called cytotrophoblasts (CTs). The balance between CT proliferation and differentiation is important for placental development. OVO-like 1 (OVOL1) is a transcription factor expressed in many epithelial lineages undergoing differentiation, including human differentiating CTs. The molecular mechanisms through which OVOL1 represses proliferation and/or promotes differentiation are unknown. We hypothesize that OVOL1 interacts with specific HDACs to repress CT proliferation. Ectopically expressing OVOL1 in wild-type yeast caused a significant growth defect, this defect was rescued by deleting class II HDACs. Ectopically expressing OVOL1 in human CT cell-line (BeWo) caused a significant increase in expression of ERVFRD1, a gene associated with cytotrophoblast differentiation, indicating that expression of OVOL1 is sufficient to trigger upregulation of at least a subset of genes that regulate CT proliferation and differentiation. Together, our findings demonstrate that OVOL1 can repress cell proliferation in yeast, a feature requiring specific HDACs, and is sufficient to at least prime CT differentiation. The combination of yeast and mammalian models provides a new experimental platform to better characterize OVOL1 function in repressing CT differentiation, providing new insights into placental development and potential therapeutics for placenta-associated diseases.
